A beta-diketone compound and a preparation method thereof

Abstract

This invention relates to the field of compound preparation technology, and in particular to a β-diketone compound and its preparation method. The preparation method includes: Step 1: Adding tetrahydrofuran and NaH to a reaction flask and stirring, then adding methyl decanoate at room temperature and raising the temperature; Step 2: Adding p-ethyl acetophenone dropwise and maintaining the temperature until it disappears; Step 3: Cooling concentrated hydrochloric acid to 5-10°C with water, then adding the solution from Step 2 dropwise to the hydrochloric acid solution and controlling the temperature at 5-30°C; Step 4: Quenching, stirring for 30 min, letting stand for 20 min, separating the organic phase, extracting the aqueous phase with tetrahydrofuran, and combining the organic phases; Step 5: Drying the organic phase with anhydrous sodium sulfate for 1 h, then filtering, and washing the filter cake; Step 6: Concentrating the filtrate under reduced pressure until no liquid flows out; Step 7: Adding methanol and ethanol to the concentrate, cooling to 15°C, adding seed crystals, stirring until crystals precipitate, then cooling to -5 to -10°C to grow crystals, and filtering to obtain the β-diketone compound. This invention improves atom utilization, is simple in process, reduces waste emissions, and is environmentally friendly.

Description

Technical Field

[0001] This invention relates to the field of compound preparation technology, and in particular to a β-diketone compound and its preparation method. Background Technology

[0002] β-Diketones are a class of compounds with wide industrial applications, such as metal extraction and polymer stabilization. β-Diketones are currently the best readily available organic stabilizers for halogenated polymers (such as PVC), and therefore these compounds have become increasingly important in industry. However, with technological advancements, the requirements for environmental friendliness, product purity, and manufacturing costs in the development of β-diketones are increasing. Using expensive stabilizers and environmentally unfriendly reagents in the polymer industry is impractical.

[0003] The most common method for preparing β-diketones is the reaction of an ester with a carbanion of a ketone, as disclosed in European Patent EP0454623A1 (CIBA-GEIGY AG) and US Patent US5015777A (Witco). However, this method has the disadvantage of leading to many side reactions, such as butenaldehyde and the formation of β-keto esters.

[0004] For example, in European patent EP0454623A1, an attempt was made to increase the yield of β-diketones by using dimethyl sulfoxide (DMSO, a relatively expensive solvent) and adding ethanol, reacting at low temperature in the presence of sodium hydroxide or an alcohol. However, the yield for esters was only moderate.

[0005] Similarly, in US Patent 5015777A, the solvent used is relatively inexpensive and easily separated from the unprocessed reaction mixture, but a large excess of ester is used. After removing the alkylbenzoate, the yield relative to the ester is only moderate to poor. In addition, the reaction mixture obtained with low reaction yield cannot be used without efficient purification, and the large excess of ester must be recycled, which is often expensive or undesirable. Summary of the Invention

[0006] The purpose of this invention is to provide a β-diketone compound and its preparation method, which can solve the above-mentioned technical problems.

[0007] This invention provides a method for preparing β-diketone compounds, comprising the following steps:

[0008] Step 1: Add tetrahydrofuran to the reaction flask, add NaH and stir, add methyl decanoate at room temperature, and then heat.

[0009] Step 2: Add p-ethyl acetophenone dropwise to the reaction flask. After the addition is complete, keep the flask warm and wait for the p-ethyl acetophenone to disappear.

[0010] Step 3: Add concentrated hydrochloric acid to water and cool it to 5-10℃ for later use. Add the reaction solution from Step 2 dropwise into the hydrochloric acid solution and control the temperature at 5-30℃.

[0011] Step 4: After quenching, stir for 30 minutes, let stand for 20 minutes, separate the upper organic phase, extract the lower aqueous phase with tetrahydrofuran again, stir for 30 minutes again, let stand for 20 minutes again, separate the liquid and separate the upper organic phase, and combine the two organic phases.

[0012] Step 5: Add anhydrous sodium sulfate to the upper organic phase obtained in step 4, stir and dry at room temperature for 1 hour, then filter and wash the filter cake with tetrahydrofuran.

[0013] Step 6: Concentrate the filtrate under reduced pressure until no liquid flows out, at which point the concentration is considered complete;

[0014] Step 7: Add methanol and ethanol to the concentrate obtained in Step 6, cool to 15°C, add seed crystals, keep warm and stir until a large amount of solid precipitates out. After precipitation, cool the liquid to -5 to -10°C, keep warm to grow crystals, and then discharge the liquid. Filter to obtain β-diketone compounds.

[0015] Preferably, in step 1, the temperature is raised to 60°C.

[0016] Preferably, the mass ratio of methyl decanoate to p-ethyl acetophenone is (1.28-1.38):1; and the mass ratio of NaH to p-ethyl acetophenone is (0.29-0.40):1.

[0017] Preferably, the p-ethyl acetophenone is added in step 2 for 1-1.5 hours and kept at that temperature for 3-4 hours.

[0018] Preferably, in step 2, TLC (EA:PE = 1:10) is used to monitor the disappearance of p-ethyl acetophenone.

[0019] Preferably, the dripping time in step 3 is 1-1.5 hours.

[0020] Preferably, in step 4, the combined organic phase is washed once more with sodium chloride aqueous solution, stirred for 30 minutes, allowed to stand for 20 minutes, and the liquid is separated to obtain the upper organic phase.

[0021] Preferably, the temperature during the vacuum concentration process in step 6 is 45-50℃.

[0022] Preferably, the mass ratio of methanol to ethanol in step 7 is 4:1.

[0023] The present invention also provides a β-diketone compound, which is prepared according to the above preparation method.

[0024] Beneficial effects:

[0025] This invention utilizes optimized reaction conditions and a catalytic system to efficiently prepare a β-diketone compound from p-ethyl acetophenone and methyl decanoate. This method improves atom utilization, simplifies the process, reduces waste emissions, and is environmentally friendly, while operating within safe limits. Furthermore, by screening different solvents and considering the properties of the target compound, an innovative method uses inexpensive and readily available mixed solvents for crystallization, obtaining the target compound with a purity exceeding 99%. Attached Figure Description

[0026] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0027] Figure 1 This is the HPLC spectrum of the product prepared in Example 1 of this invention;

[0028] Figure 2 The HPLC spectrum of the product prepared in Example 2 of this invention;

[0029] Figure 3 The 1H NMR spectrum of the product prepared in Example 2 of this invention;

[0030] Figure 4 The carbon NMR spectrum of the product prepared in Example 2 of this invention;

[0031] Figure 5 The HPLC spectrum of the product prepared in Example 3 of this invention;

[0032] Figure 6 The HPLC spectrum of the product prepared in Example 4 of this invention;

[0033] Figure 7 The HPLC spectrum of the product prepared in Example 5 of this invention;

[0034] Figure 8 The HPLC spectrum of the product prepared in Comparative Example 1 of this invention is shown below.

[0035] Figure 9 The HPLC spectrum of the product prepared in Comparative Example 2 of this invention is shown below.

[0036] Figure 10 The HPLC spectrum of the product prepared in Comparative Example 3 of this invention is shown.

[0037] Figure 11 The HPLC spectrum of the product prepared in Comparative Example 4 of this invention is shown.

[0038] Figure 12 The HPLC spectrum of the product prepared in Comparative Example 5 of this invention is shown. Detailed Implementation

[0039] It should be noted that the following detailed descriptions are illustrative and intended to provide further explanation of this application. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains.

[0040] It should be noted that the terminology used herein is for the purpose of describing particular implementations only and is not intended to limit the exemplary implementations according to this application. As used herein, the singular form includes the plural form unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this description, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0041] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0042] The synthesis process of the β-diketone compounds of this invention is as follows:

[0043]

[0044] Example 1:

[0045] Add 60 ml of THF (purchased from Sinopharm Chemical Reagent Co., Ltd., hereinafter referred to as "Sinopharm") and 4.0 g (0.17 mol) of sodium hydride (purchased from Sinopharm) to a 250 ml four-necked flask. Adjust the material temperature to 25 °C with a mechanical stirrer. Stir for 10 min to disperse evenly. Then, add 13.2 g (0.071 mol) of methyl decanoate, stir and heat to 60 °C. Add 10 g (0.067 mol) of p-ethyl acetophenone at a uniform rate through a constant pressure dropping funnel over a period of 1.5 h. Stir at 60 °C for 4 h and monitor the reaction progress. After the reaction is complete, cool to 10 °C and set aside for later use.

[0046] Add 20g of concentrated hydrochloric acid and 50g of water to another reaction flask, cool to 10℃, and add the reacted solution dropwise into the hydrochloric acid solution, adjusting the pH of the solution to 2-3. Maintain the temperature between 5℃ and 30℃ and add the solution dropwise for 1.5 hours. After the addition is complete, stir at 25℃-30℃ for 30 minutes, let stand for 20 minutes, separate the liquids, collect the upper organic phase, and extract the lower aqueous phase once more with 20g of THF. Stir for 30 minutes, let stand for 20 minutes, separate the liquids, collect the upper organic phase, and combine the two organic phases. Wash the organic phase once more with sodium chloride aqueous solution, stir for 30 minutes, let stand for 20 minutes, separate the liquids, and collect the upper organic phase. Add 5g of anhydrous sodium sulfate to the upper organic phase, stir and dry at room temperature for 1 hour, then filter. Wash the filter cake with 10g of THF. Concentrate the filtrate under reduced pressure at 50℃ until no liquid flows out, which is considered as the concentration is complete. Add 72g of methanol and 18g of ethanol to the concentrated oily substance, cool to 15℃, add seed crystals, and stir while keeping warm until a large amount of solid precipitates. After precipitation, cool the solution to -10℃, keep warm to grow crystals for 1 hour, and then discharge the material. Filter or centrifuge to obtain wet powder, and vacuum dry to obtain 17.3g of dry product, with a yield of 85% and a purity of 98.3%.

[0047] Example 2

[0048] Add 60 ml of THF (purchased from Sinopharm Chemical Reagent Co., Ltd., hereinafter referred to as "Sinopharm") and 3.4 g (0.14 mol) of sodium hydride (purchased from Sinopharm) to a 250 ml four-necked flask. Adjust the material temperature to 25 °C with a mechanical stirrer. Stir for 10 min to disperse evenly. Then, add 13.2 g (0.071 mol) of methyl decanoate, stir and heat to 60 °C. Add 10 g (0.067 mol) of p-ethyl acetophenone at a constant pressure dropping funnel over a period of 1.5 h. Stir at 60 °C for 4 h and monitor the reaction progress. After the reaction is complete, cool to 10 °C and set aside for later use.

[0049] Add 20g of concentrated hydrochloric acid and 50g of water to another reaction flask, cool to 10℃, and add the reacted solution dropwise into the hydrochloric acid solution, adjusting the pH of the solution to 2-3. Maintain the temperature between 5℃ and 30℃ and add the solution dropwise for 1.5 hours. After the addition is complete, stir at 25℃-30℃ for 30 minutes, let stand for 20 minutes, separate the liquids, collect the upper organic phase, and extract the lower aqueous phase once more with 20g of THF. Stir for 30 minutes, let stand for 20 minutes, separate the liquids, collect the upper organic phase, and combine the two organic phases. Wash the organic phase once more with sodium chloride aqueous solution, stir for 30 minutes, let stand for 20 minutes, separate the liquids, and collect the upper organic phase. Add 5g of anhydrous sodium sulfate to the upper organic phase, stir and dry at room temperature for 1 hour, then filter. Wash the filter cake with 10g of THF. Concentrate the filtrate under reduced pressure at 50℃ until no liquid flows out, which is considered as the concentration is complete. Add 72g of methanol and 18g of ethanol to the concentrated oily substance, cool to 15℃, add seed crystals, and stir while keeping warm until a large amount of solid precipitates. After precipitation, cool the liquid to -10℃, keep warm to grow crystals for 1 hour, and then discharge the material. Filter or centrifuge to obtain wet powder, and vacuum dry to obtain 19.2g of dry product, with a yield of 95% and a purity of 99.5%.

[0050] Example 3

[0051] Add 60 ml of THF (purchased from Sinopharm Chemical Reagent Co., Ltd., hereinafter referred to as "Sinopharm") and 2.9 g (0.12 mol) of sodium hydride (purchased from Sinopharm) to a 250 ml four-necked flask. Adjust the material temperature to 25 °C with a mechanical stirrer. Stir for 10 min to disperse evenly. Then, add 13.2 g (0.071 mol) of methyl decanoate, stir and heat to 60 °C. Add 10 g (0.067 mol) of p-ethyl acetophenone at a uniform rate through a constant pressure dropping funnel over a period of 1.5 h. Stir at 60 °C for 4 h and monitor the reaction progress. After the reaction is complete, cool to 10 °C and set aside.

[0052] Add 20g of concentrated hydrochloric acid and 50g of water to another reaction flask, cool to 10℃, and add the reacted solution dropwise into the hydrochloric acid solution, adjusting the pH of the solution to 2-3. Maintain the temperature between 5℃ and 30℃ and add the solution dropwise for 1.5 hours. After the addition is complete, stir at 25℃-30℃ for 30 minutes, let stand for 20 minutes, separate the liquids, collect the upper organic phase, and extract the lower aqueous phase once more with 20g of THF. Stir for 30 minutes, let stand for 20 minutes, separate the liquids, collect the upper organic phase, and combine the two organic phases. Wash the organic phase once more with sodium chloride aqueous solution, stir for 30 minutes, let stand for 20 minutes, separate the liquids, and collect the upper organic phase. Add 5g of anhydrous sodium sulfate to the upper organic phase, stir and dry at room temperature for 1 hour, then filter. Wash the filter cake with 10g of THF. Concentrate the filtrate under reduced pressure at 50℃ until no liquid flows out, which is considered as the concentration is complete. Add 72g of methanol and 18g of ethanol to the concentrated oily substance, cool to 15℃, add seed crystals, and stir while keeping warm until a large amount of solid precipitates. After precipitation, cool the solution to -10℃, keep warm to grow crystals for 1 hour, and then discharge the material. Filter or centrifuge to obtain wet powder, and vacuum dry to obtain 18.0g of dry product, with a yield of 89% and a purity of 99.1%.

[0053] Example 4

[0054] Add 60 ml of THF (purchased from Sinopharm Chemical Reagent Co., Ltd., hereinafter referred to as "Sinopharm") and 3.4 g (0.14 mol) of sodium hydride (purchased from Sinopharm) to a 250 ml four-necked flask. Adjust the material temperature to 25 °C with a mechanical stirrer. Stir for 10 min to disperse evenly. Then, add 12.8 g (0.069 mol) of methyl decanoate, stir and heat to 60 °C. Add 10 g (0.067 mol) of p-ethyl acetophenone at a uniform rate through a constant pressure dropping funnel over a period of 1.5 h. Stir at 60 °C for 4 h and monitor the reaction progress. After the reaction is complete, cool to 10 °C and set aside.

[0055] Add 20g of concentrated hydrochloric acid and 50g of water to another reaction flask, cool to 10℃, and add the reacted solution dropwise into the hydrochloric acid solution, adjusting the pH of the solution to 2-3. Maintain the temperature between 5℃ and 30℃ and add the solution dropwise for 1.5 hours. After the addition is complete, stir at 25℃-30℃ for 30 minutes, let stand for 20 minutes, separate the liquids, collect the upper organic phase, and extract the lower aqueous phase once more with 20g of THF. Stir for 30 minutes, let stand for 20 minutes, separate the liquids, collect the upper organic phase, and combine the two organic phases. Wash the organic phase once more with sodium chloride aqueous solution, stir for 30 minutes, let stand for 20 minutes, separate the liquids, and collect the upper organic phase. Add 5g of anhydrous sodium sulfate to the upper organic phase, stir and dry at room temperature for 1 hour, then filter. Wash the filter cake with 10g of THF. Concentrate the filtrate under reduced pressure at 50℃ until no liquid flows out, which is considered as the concentration is complete. Add 72g of methanol and 18g of ethanol to the concentrated oily substance, cool to 15℃, add seed crystals, and stir while keeping warm until a large amount of solid precipitates. After precipitation, cool the liquid to -10℃, keep warm to grow crystals for 1 hour, and then discharge the material. Filter or centrifuge to obtain wet powder, and vacuum dry to obtain 18.0g of dry product, with a yield of 89% and a purity of 99.0%.

[0056] Example 5

[0057] Add 60 ml of THF (purchased from Sinopharm Chemical Reagent Co., Ltd., hereinafter referred to as "Sinopharm") and 3.4 g (0.14 mol) of sodium hydride (purchased from Sinopharm) to a 250 ml four-necked flask. Adjust the material temperature to 25 °C with a mechanical stirrer. Stir for 10 min to disperse evenly. Then, add 13.8 g (0.074 mol) of methyl decanoate, stir and heat to 60 °C. Add 10 g (0.067 mol) of p-ethyl acetophenone at a uniform rate through a constant pressure dropping funnel over a period of 1.5 h. Stir at 60 °C for 4 h and monitor the reaction progress. After the reaction is complete, cool to 10 °C and set aside.

[0058] Add 20g of concentrated hydrochloric acid and 50g of water to another reaction flask, cool to 10℃, and add the reacted solution dropwise into the hydrochloric acid solution, adjusting the pH of the solution to 2-3. Maintain the temperature between 5℃ and 30℃ and add the solution dropwise for 1.5 hours. After the addition is complete, stir at 25℃-30℃ for 30 minutes, let stand for 20 minutes, separate the liquids, collect the upper organic phase, and extract the lower aqueous phase once more with 20g of THF. Stir for 30 minutes, let stand for 20 minutes, separate the liquids, collect the upper organic phase, and combine the two organic phases. Wash the organic phase once more with sodium chloride aqueous solution, stir for 30 minutes, let stand for 20 minutes, separate the liquids, and collect the upper organic phase. Add 5g of anhydrous sodium sulfate to the upper organic phase, stir and dry at room temperature for 1 hour, then filter. Wash the filter cake with 10g of THF. Concentrate the filtrate under reduced pressure at 50℃ until no liquid flows out, which is considered as the concentration is complete. Add 72g of methanol and 18g of ethanol to the concentrated oily substance, cool to 15℃, add seed crystals, and stir while keeping warm until a large amount of solid precipitates. After precipitation, cool the solution to -10℃, keep warm to grow crystals for 1 hour, and then discharge the material. Filter or centrifuge to obtain wet powder, and vacuum dry to obtain 19.1g of dry product, with a yield of 94% and a purity of 99.4%.

[0059] Comparative Example 1

[0060] The target compound was prepared according to the method of Example 2, except that an equal amount of DMF was added to the four-necked flask instead of tetrahydrofuran, and the yield of the target compound was 93%.

[0061] Comparative Example 2

[0062] The target compound was prepared according to the method of Example 2, except that an equal amount of sodium methoxide was added to the four-necked flask instead of sodium hydride. Chromatographic analysis of the organic layer showed that the yield of the target compound was 55%.

[0063] Comparative Example 3

[0064] The target compound was prepared according to the method in Example 2, except that an equal amount of sodium tert-butoxide was added to the four-necked flask instead of sodium hydride. Chromatographic analysis of the organic layer showed that the yield of the target compound was 75%.

[0065] Comparative Example 4

[0066] The target compound was prepared according to the method in Example 2, except that the crystallization solvent was changed from a mixture of methanol and ethanol to methanol. The yield of the target compound was 75%, and the purity was 99.6%.

[0067] Comparative Example 5

[0068] The target compound was prepared according to the method in Example 2, except that the crystallization solvent was changed from a mixture of methanol and ethanol to ethanol. The yield of the target compound was 96% and the purity was 97.5%.

[0069] As can be seen from the comparison of Examples 1-3, the method for preparing the target compound described in this invention, using the amount of sodium hydride shown in Example 2, yields the highest yield.

[0070] As can be seen from the comparison of Examples 1-6, the method for preparing the target compound described in this invention achieves the highest yield using the sodium hydride and methyl decanoate feed amounts shown in Example 2.

[0071] As can be seen from the comparison between Example 2 and Comparative Experiment 1, the method for preparing the target compound described in this invention uses DMF and THF as solvents with comparable yields, but THF is preferred considering the recovery cost.

[0072] As can be seen from the comparison of Example 2 and Comparative Experiments 2 and 3, the method for preparing the target compound described in this invention using sodium hydride as shown in Example 2 yields the highest yield.

[0073] As can be seen from the comparison of Example 2 and Comparative Experiments 4 and 5, the method for preparing the target compound described in this invention, using the crystallization solvent shown in Example 2, yields the highest yield.

[0074] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing a β-diketone compound, characterized in that, Includes the following steps: Step 1: Add tetrahydrofuran to the reaction flask, add NaH and stir, add methyl decanoate at room temperature, and then heat to 60°C; Step 2: Add p-ethyl acetophenone dropwise to the reaction flask. After the addition is complete, keep the flask warm and wait for the p-ethyl acetophenone to disappear. The addition time for p-ethyl acetophenone is 1-1.5 hours, and the flask is kept warm for 3-4 hours. The mass ratio of methyl decanoate to p-ethyl acetophenone is (1.28-1.38):

1. Step 3: Add concentrated hydrochloric acid to water and cool it to 5-10℃ for later use. Add the reaction solution from Step 2 dropwise into the hydrochloric acid solution and control the temperature at 5-30℃. Step 4: After quenching, stir for 30 minutes, let stand for 20 minutes, separate the upper organic phase, extract the lower aqueous phase with tetrahydrofuran again, stir for 30 minutes again, let stand for 20 minutes again, separate the liquid and separate the upper organic phase, and combine the two organic phases. Step 5: Add anhydrous sodium sulfate to the upper organic phase obtained in step 4, stir and dry at room temperature for 1 hour, then filter and wash the filter cake with tetrahydrofuran. Step 6: Concentrate the filtrate under reduced pressure until no liquid flows out, at which point the concentration is considered complete; Step 7: Add methanol and ethanol to the concentrate obtained in Step 6, cool to 15°C, add seed crystals, and stir while maintaining the temperature until a large amount of solid precipitates. After precipitation, cool the liquid to -5~-10°C, maintain the temperature to grow crystals, and then discharge the material. Filter to obtain β-diketone compounds. The structure of the compounds is shown below: .

2. The method for preparing β-diketone compounds according to claim 1, characterized in that, In step 2, TLC is used to monitor the disappearance of p-ethyl acetophenone, with EA:PE = 1:

10.

3. The method for preparing β-diketone compounds according to claim 1, characterized in that, The dripping time in step 3 is 1-1.5 hours.

4. The method for preparing β-diketone compounds according to claim 1, characterized in that, In step 4, the combined organic phases are washed once more with sodium chloride aqueous solution, stirred for 30 minutes, allowed to stand for 20 minutes, and the liquid-liquid phase is separated.

5. The method for preparing β-diketone compounds according to claim 1, characterized in that, The temperature during the vacuum concentration process in step 6 is 45-50℃.

6. The method for preparing β-diketone compounds according to claim 1, characterized in that, In step 7, the mass ratio of methanol to ethanol is 4:1.

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